Intradermal delivery of modified mRNA encoding VEGF-A in patients with type 2 diabetes

Gan, Li-Ming, 1969 (author): Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine

Lagerstrom-Fermer, M. (author)

Carlsson, L. G. (author)

Arfvidsson, C. (author)

Egnell, A. C. (author)

Rudvik, A. (author)

Kjaer, M. (author)

Collen, A. (author)

Thompson, J. D. (author)

Joyal, J. (author)

Chialda, L. (author)

Koernicke, T. (author)

Fuhr, R. (author)

Fritsche-Danielson, R. (author)

(creator_code:org_t)

2019-02-20
2019
English.
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10

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Abstract Subject headings

Chemically modified mRNA is an efficient, biocompatible modality for therapeutic protein expression. We report a first-time-in-human study of this modality, aiming to evaluate safety and potential therapeutic effects. Men with type 2 diabetes mellitus (T2DM) received intradermal injections of modified mRNA encoding vascular endothelial growth factor A (VEGF-A) or buffered saline placebo (ethical obligations precluded use of a non-translatable mRNA control) at randomized sites on the forearm. The only causally treatment-related adverse events were mild injection-site reactions. Skin microdialysis revealed elevated VEGF-A protein levels at mRNA-treated sites versus placebo-treated sites from about 4-24 hours post-administration. Enhancements in basal skin blood flow at 4 hours and 7 days post-administration were detected using laser Doppler fluximetry and imaging. Intradermal VEGF-A mRNA was well tolerated and led to local functional VEGF-A protein expression and transient skin blood flow enhancement in men with T2DM. VEGF-A mRNA may have therapeutic potential for regenerative angiogenesis.

By the author/editor: Gan, Li-Ming, 19 ...; Lagerstrom-Ferme ...; Carlsson, L. G.; Arfvidsson, C.; Egnell, A. C.; Rudvik, A.; show more...; Kjaer, M.; Collen, A.; Thompson, J. D.; Joyal, J.; Chialda, L.; Koernicke, T.; Fuhr, R.; Chien, K. R.; Fritsche-Daniels ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cardiac and Card ...

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